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Study to Compare the Pharmacokinetics Profiles of Four Racecadotril Products

Primary Purpose

Diarrhea

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Racecadotril

About this trial

This is an interventional basic science trial for Diarrhea focused on measuring Antidiarrheals

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Male or female subjects (equal numbers of males and females)
Volunteers aged of at least 18 years but not older than 55 years
Subjects will have a Body Mass Index (BMI) within protocol-specified parameters.
Non- or ex-smokers; an ex-smoker being defined as someone who completely stopped smoking for at least 12 months before day 1 of this study.
Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance
Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations Has signed and dated the informed consent document, indicating that the subject has been informed of all pertinent aspects of the study
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

Seated pulse rate and blood pressure within protocol-specified parameters.
Relationship to persons involved directly with the conduct of the study (i.e., principal investigator; sub-investigators; study coordinators; other study personnel; employees or contractors of the sponsor or Johnson & Johnson subsidiaries; and the families of each)
Females who are pregnant or are lactating
Females of childbearing potential or males with a female partner of childbearing potential who refuse to use an acceptable contraceptive regimen throughout the entire duration of the study
History of significant hypersensitivity to racecadotril or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
Use of certain drugs/medications within protocol-specified timeframes
Medical history or condition that may, per protocol or in the opinion of the investigator, adversely affect the safety of the study subject or compromise study results.

Sites / Locations

Algorithme Pharma Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

FCT

RPB

TFT

TFR

Arm Description

A single 2 x100 mg dose of an experimental Racecadotril Film-coated tablet (FCT) administered orally with 240 ml of water, with a 7- day washout between visits.

A single 2 x100 mg dose of an experimental Racecadotril Powder Blend administered orally with 240 ml of water, with a 7- day washout between visits.

A single 2 x 100 mg dose of a marketed Tiorfast® capsule administered orally with 240 ml of water, with a 7-day washout between visits.

A single 175 mg dose of a marketed Tiorfanor® 175 mg FCT administered orally with 240 ml of water, with a 7-day washout between visits.

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration

Maximum Observed Plasma Concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered, measured in nanograms/milliliter (ng/mL)

AUC(0-t)

AUC(0-t) is the area under the plasma concentration verses time curve from start of drug administration until the time of the last measurable plasma concentration, calculated as hour*nanograms (ng) per milliliter (mL).

AUC(0-∞)

AUC (0-∞) is the area under the plasma concentration-vs.-time curve from start of drug administration until infinity.

Secondary Outcome Measures

Time of Maximum Concentration

The time at which maximum concentration is reached (Tmax)

Terminal Elimination Rate Constant

The Terminal Elimination Rate Constant (Lamda z) is the time required to eliminate half the administered dose

Terminal Phase Plasma Half-Life

Terminal phase plasma half-life (t ½) is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, rather than the time required to eliminate half the administered dose.

Lag Time

The time delay between drug administration and the quantification of absorption

Full Information

NCT ID

NCT01476683

First Posted

November 17, 2011

Last Updated

July 6, 2012

Sponsor

McNeil AB

1. Study Identification

Unique Protocol Identification Number

NCT01476683

Brief Title

Study to Compare the Pharmacokinetics Profiles of Four Racecadotril Products

Official Title

An Open-Label, Fasting, Crossover, Single-Dose Pharmacokinetic Study of Four Formulations of Racecadotril

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Completed

Study Start Date

December 2011 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

McNeil AB

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study is designed to compare the pharmacokinetics of four products used for treatment of acute diarrhea.

Detailed Description

The study will be a single dose, randomized, four -way, four-sequence crossover study in 24 healthy subjects, with equal numbers of males and females (minimum of 10 of either gender). Subjects who drop out will not be replaced. The four doses of medication given in the study (a single dose in each of the four study periods) will be separated by a washout period of at least 7 calendar days. In each study period, 17 blood samples for pharmacokinetic analysis will be taken over 12 hours. Blood samples will be centrifuged and concentrations of thiorphan (the active metabolite) in plasma will be measured using a validated chromatographic assay. Pharmacokinetic parameters will be calculated from plasma concentration data.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diarrhea

Keywords

Antidiarrheals

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FCT

Arm Type

Experimental

Arm Description

A single 2 x100 mg dose of an experimental Racecadotril Film-coated tablet (FCT) administered orally with 240 ml of water, with a 7- day washout between visits.

Arm Title

RPB

Arm Type

Experimental

Arm Description

A single 2 x100 mg dose of an experimental Racecadotril Powder Blend administered orally with 240 ml of water, with a 7- day washout between visits.

Arm Title

TFT

Arm Type

Active Comparator

Arm Description

A single 2 x 100 mg dose of a marketed Tiorfast® capsule administered orally with 240 ml of water, with a 7-day washout between visits.

Arm Title

TFR

Arm Type

Active Comparator

Arm Description

A single 175 mg dose of a marketed Tiorfanor® 175 mg FCT administered orally with 240 ml of water, with a 7-day washout between visits.

Intervention Type

Drug

Intervention Name(s)

Racecadotril

Other Intervention Name(s)

Not yet marketed

Intervention Description

Film-coated tablet

Intervention Type

Drug

Intervention Name(s)

Racecadotril

Other Intervention Name(s)

Not yet marketed

Intervention Description

Racecadotril Powder Blend

Intervention Type

Drug

Intervention Name(s)

Racecadotril

Other Intervention Name(s)

Tiorfast®

Intervention Description

Marketed Capsule

Intervention Type

Drug

Intervention Name(s)

Racecadotril

Other Intervention Name(s)

Tiorfanor®

Intervention Description

Marketed Film-coated Tablet

Primary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration

Description

Time Frame

Pre-dose and 0.25, 0.5, 0.75, 1, 1.25 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours post drug administration

Title

AUC(0-t)

Description

Time Frame

Pre-dose and 0.25, 0.5, 0.75, 1, 1.25 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours post drug administration

Title

AUC(0-∞)

Description

AUC (0-∞) is the area under the plasma concentration-vs.-time curve from start of drug administration until infinity.

Time Frame

Pre-dose and 0.25, 0.5, 0.75, 1, 1.25 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours post drug administration

Secondary Outcome Measure Information:

Title

Time of Maximum Concentration

Description

The time at which maximum concentration is reached (Tmax)

Time Frame

During 12 hours post-dose

Title

Terminal Elimination Rate Constant

Description

The Terminal Elimination Rate Constant (Lamda z) is the time required to eliminate half the administered dose

Time Frame

During 12 hours post-dose

Title

Terminal Phase Plasma Half-Life

Description

Time Frame

During 12 hours post-dose

Title

Lag Time

Description

The time delay between drug administration and the quantification of absorption

Time Frame

During 12 hours post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female subjects (equal numbers of males and females) Volunteers aged of at least 18 years but not older than 55 years Subjects will have a Body Mass Index (BMI) within protocol-specified parameters. Non- or ex-smokers; an ex-smoker being defined as someone who completely stopped smoking for at least 12 months before day 1 of this study. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations Has signed and dated the informed consent document, indicating that the subject has been informed of all pertinent aspects of the study Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: Seated pulse rate and blood pressure within protocol-specified parameters. Relationship to persons involved directly with the conduct of the study (i.e., principal investigator; sub-investigators; study coordinators; other study personnel; employees or contractors of the sponsor or Johnson & Johnson subsidiaries; and the families of each) Females who are pregnant or are lactating Females of childbearing potential or males with a female partner of childbearing potential who refuse to use an acceptable contraceptive regimen throughout the entire duration of the study History of significant hypersensitivity to racecadotril or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs Use of certain drugs/medications within protocol-specified timeframes Medical history or condition that may, per protocol or in the opinion of the investigator, adversely affect the safety of the study subject or compromise study results.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elisabeth Kruse, PhD

Organizational Affiliation

McNeil AB

Official's Role

Study Director

Facility Information:

Facility Name

Algorithme Pharma Inc.

City

Mount-Royal

State/Province

Quebec

ZIP/Postal Code

H3P 3P1

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

Study to Compare the Pharmacokinetics Profiles of Four Racecadotril Products

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